Silver nanoplate compositions and methods

ABSTRACT

Embodiments of the present invention relate to methods for preparing high optical density solutions of nanoplates, such as silver nanoplates or silver platelet nanoparticles, and to nanoparticles, solutions and substrates prepared by said methods. The process can include the addition of stabilizing agents (e.g., chemical or biological agents bound or otherwise linked to the nanoparticle surface) that stabilize the nanoparticle before, during, and/or after concentration, thereby allowing for the production of a stable, high optical density solution of silver nanoplates. The process can also include increasing the concentration of silver nanoplates within the solution, and thus increasing the solution optical density.

INCORPORATION BY REFERENCE TO ANY PRIORITY APPLICATIONS

This application is a continuation of U.S. application Ser. No.14/048,996 filed Oct. 8, 2013, which claims the benefit of priority fromU.S. Provisional Application 61/795,149, filed on Oct. 11, 2012, each ofwhich is incorporated by reference in its entirety. Any and allapplications for which a foreign or domestic priority claim isidentified in the Application Data Sheet as filed with the presentapplication are hereby incorporated by reference under 37 CFR 1.57.

BACKGROUND

1. Field of the Invention

Various embodiments of the invention relate to methods for preparinghigh optical density solutions of silver platelet nanoparticles (e.g.,nanoplates) and to nanoparticles, solutions and substrates prepared bysaid methods.

2. Description of the Related Art

Nanoparticles, including nanospheres, nanorods, nanowires, nanocubes,nanoplates, as well as other shapes can be synthesized from a range ofmaterials. Nanoparticles made from metals including gold and silver haveunique optical properties which can be tuned to interact with lightthroughout the electromagnetic spectrum due to the localized surfaceplasmon resonance supported by these nanomaterials. Technologies thattake advantage of the unique optical properties of silver nanoparticles,(e.g., such as silver nanoplates), include, but are not limited to,diagnostic, photonic, medical, and obscurant technologies. A subset ofthese technologies including photothermal tumor ablation, hair removal,acne treatment, wound healing, and antimicrobial applications amongothers, may use solutions of nanoparticles with high optical densities.Silver platelet nanoparticles, which are also known as silver nanoplatesor silver nanoprisms, are of particular interest for technologies thatutilize nanoparticle optical properties due to their tunable spectralpeaks and extremely high optical efficiencies. While methods tofabricate silver platelet nanoparticles via photoconversion (Jin et al.2001; Jin et al. 2003), pH-controlled photoconversion (Xue 2007),thermal growth (Hao et al. 2004; Hao 2002; He 2008; Metraux 2005),templated growth (Hao et al. 2004; Hao 2002), and seed mediated growth(Aherne 2008; Chen; Carroll 2003; Chen; Carroll 2002, 2004; Chen et al.2002; He 2008; Le Guevel 2009; Xiong et al. 2007) have been developed,these methods generate relatively dilute solutions with correspondinglylow visible and near-infrared optical densities, (e.g., such as opticaldensities of less than 10 cm⁻¹, such as 1-9 cm⁻¹, 5-10 cm⁻¹).

SUMMARY

For many silver nanoplate applications, a more concentrated solution ofthe silver nanoplates is of utility and can be particularlyadvantageous. In some instances, when the as-fabricated solutions ofsilver nanoplates are concentrated to yield a higher particle densityunder previously developed methods, the shape of the particle canundergo a change resulting in a shift in the solution opticalproperties. In many cases, these changes result in an undesirabledegradation of their optical properties. Accordingly, severalembodiments of the present invention provide methods for preparing highoptical density solutions of silver nanoplates from dilute silvernanoplate solutions that substantially or fully preserve the opticalproperties of as-fabricated silver nanoplates when the particleconcentration is increased. The high optical density solutions of silvernanoplates can be exposed to substrates to generate nanoplate compositeswith high loading levels.

Various embodiments of the invention provide a method for preparing highoptical density solutions of silver platelet nanoparticles, as well asthe nanoparticles and solutions prepared by those methods. In oneembodiment, the process comprises the replacement of one or moreoriginal components (e.g., chemical or biological agents) bound, orotherwise coupled to, the nanoparticle surface with a stabilizing agent.The stabilizing agent can be a biological or chemical agent thatstabilizes the nanoplates before, during, and/or after concentration,thereby allowing for the production of a stable, high optical densitysolution of silver nanoplates. In one embodiment, the process alsocomprises a method of increasing the concentration of silver nanoplateswithin the solution, and thus increasing the solution optical density.In several embodiments, the stability (e.g., the characteristics of thenanoparticles in the solution, such as shape, size, optical properties,peak response, plasmonic properties, etc.) of the high optical densitysolution is unaffected or substantially unaffected during the process.

In one embodiment, a high optical density solution comprises silvernanoplates that have been stabilized with stabilizing agents (e.g.,surface bound molecules chemical agents, and/or biological agents). Invarious embodiments, a solution of silver platelet nanoparticles (e.g.,silver nanoplates) have been surface functionalized with chemical orbiological agents that are physisorbed to the surface, molecularly boundto the surface through specific interactions, or encapsulate eachnanoplate on its surface.

In one embodiment, a high optical density solution of silver nanoplatesis associated with a substrate. In one embodiment, a portion of thenanoplates in solution bind to the substrate to create ananoplate-substrate composite. The high optical density solutions ofsilver nanoplates can be exposed to substrates to generate nanoplatecomposites where a substantial portion of the surface area of asubstrate is coated with nanoplates. In some embodiments the substratecomprises fibers, cloth, mesh, bandages, socks, wraps, other articles ofclothing, sponges, high porosity substrates, particles with edge lengthsgreater than 1 micron, beads, hair, skin, paper, absorbent polymers,foam, wood, cork, slides, roughened surfaces, biocompatible substrates,filters, and/or medical implants.

In several embodiments, a process for increasing the optical density ofa solution of stable, silver nanoplates comprises the following: (i)providing a solution comprising silver nanoplates having a plate shape,a first extinction spectra, and a first peak optical density between0.1-10 cm⁻¹; (ii) adding a concentration stabilizing chemical agent tothe solution of silver nanoplates; and (iii) increasing theconcentration of silver nanoplates using tangential flow filtration,thereby increasing the optical density of the solution to a second peakoptical density greater than 10 cm⁻¹, wherein the silver nanoplatescomprise the plate shape and the first extinction spectra at the opticaldensity greater than 10 cm⁻¹.

In various embodiments, the stabilizing agent comprises or consistsessentially of at least one of the group consisting of polyvinylpyrollidone, polyvinyl alcohol, polyethylene glycol, and dextran. Invarious embodiments, the stabilizing agent comprises or consistsessentially of at least one of the group consisting of polysulphonates,ethylene oxides, phenols, and carbohydrates. In one embodiment, theconcentration stabilizing chemical agent is a water soluble polymer. Inone embodiment, the concentration stabilizing chemical agent is a metalor metalloid oxide. In one embodiment, the stabilizing chemical agent isa silicon dioxide shell. In various embodiment, the silicon dioxideshell ranges in thickness from 1 nm to 100 nm. In one embodiment, thestabilizing chemical agent is a titanium dioxide shell. In variousembodiments, a combination of stabilizing agents are used.

In various embodiments, the process further comprises adding any of thegroup selected from an acid, a base, and a buffering agent to thesolution. In one embodiment, the silver nanoplates have an aspect ratioof between 1.5 and 25. In one embodiment, the nanoplate has an edgelength between 10 nm and 250 nm. In some embodiments, the solution ofsilver nanoplates is formed using a seed mediated growth method. In oneembodiment, the concentration of silver nanoplates is washed withbetween 1 and 5 wash volumes after increasing the concentration usingtangential flow filtration. In one embodiment, the solution of silvernanoplates is incubated with a substrate.

In various embodiments, a process for generating a solution of silvernanoplates with high optical density comprises the following: (i)providing a solution of silver nanoplates with a first peak opticaldensity between 0.1-10 cm⁻¹, (ii) adding a concentration stabilizingchemical agent to the solution of silver nanoplates; (iii) adding abuffer to the solution of silver nanoplates; and (iv) increasing theconcentration of the silver nanoplates to increase the optical densityof the solution greater than 10 cm⁻¹.

In one embodiment, the concentration stabilizing chemical agentcomprises a derivative of a vinyl polymer. In one embodiment, thepolymer is polyvinyl alcohol (PVA). In one embodiment, the polymer ispolyvinyl pyrrolidone (PVP). In one embodiment, the process furthercomprises adding one of the group consisting of sodium bicarbonate andsodium borate to the solution.

In several embodiments, a process for generating a solution of silvernanoplates with extremely high optical density comprises the following:(i) adding a concentration stabilizing chemical agent to a solution ofsilver nanoplates or precursor reagents and (ii) increasing theconcentration of silver nanoplates to increase the optical density ofthe solution.

In various embodiments, the silver nanoplates have an aspect ratio ofbetween 1.5 and 25 (e.g., 1.5-10, 25-50); and/or the nanoplate has anedge length between about 10 nm and 250 nm (e.g., 50-250, 65-100 nm);and/or the nanoplate is triangular in cross section; and/or thenanoplate is circular in cross section. In one embodiment, the perimeterof the nanoplate cross section has between 4 and 8 edges (e.g., 4, 5, 6,7, 8). In various embodiments, the solution of silver nanoplates isformed using one or more of a photoconversion method, a pH-controlledphotoconversion method, a thermal growth method, a seed mediated growthmethod, and/or a solution comprising a shape stabilizing agent or agentsand a silver source. In various embodiments, chemical or biologicalagents, and/or electromagnetic radiation, and/or heat, or a combinationthereof are used to reduce the silver source. In one embodiment, thesolution of silver nanoplates is formed from some combination of areducing agent, a shape stabilizing agent, a light source, a heatsource, and a silver source.

In one embodiment, an acid, base, or buffering agent is added to changethe solution pH. In various embodiments, the concentration stabilizingchemical agent is added prior to, during, and/or after the formation ofthe silver nanoplates. In one embodiment, the concentration stabilizingchemical agent acts as a shape stabilizing agent. In one embodiment, theconcentration stabilizing chemical agent acts as a reducing agent. Inone embodiment, the concentration stabilizing chemical agent acts as anagent to change the solution pH.

In one embodiment, the concentration stabilizing chemical agent is awater soluble polymer. In various embodiments, the polymer is any one ormore of a derivative of polysulfonate, sodium polystyrene sulfonate, aderivative of a vinyl polymer, and a polyvinyl alcohol (PVA). In variousembodiments, the PVA has a molecular weight of less than about 80,000Dalton (e.g., 1,000-50,000, 25,000-75,000 Dalton), between about 80,000Dalton and 120,000 Dalton (e.g., 85,000-95,000, 100,000-110,000 Dalton),and/or more than about 120,000 Dalton (e.g., 150,000-300,000 Dalton). Inone embodiment, the polymer is polyvinylpyrrolidone (PVP). In variousembodiments, the PVP has a molecular weight of less than about 20,000Dalton (e.g., 2,000-12,000 Dalton), more than about 20,000 Dalton (e.g.,35,000-400,000 Dalton), between about 20,000 Dalton and 60,000 Dalton(e.g., 40,000-55,000 Dalton), and/or more than about 60,000 Dalton(e.g., 70-100,000, 90-150,000 Dalton). In one embodiment, the polymer isan ethylene oxide derivative.

In one embodiment, the polymer is a polyethylene glycol (PEG). Invarious embodiments, the PEG has a molecular weight of less than about5,000 Dalton (e.g., 200-3,000, 1,000-4,500 Dalton), between about 5,000Dalton and 10,000 Dalton (e.g., 7,000-8,000, 6,000-7,500 Dalton), and/ormore than about 10,000 Dalton (e.g., 12,000-35,000, 18,000-45,000Dalton). In one embodiment, the PEG contains a single functional group.In one embodiment, the PEG contains more than one functional group(e.g., two, three, or more functional groups). In one embodiment, thefunctional group or groups comprise any of an amine, thiol, acrylate,alkyne, maleimide, silane, azide, hydroxyl, lipid, disulfide,fluorescent molecule, and/or biotin. In one embodiment, the functionalgroup or groups can be any one or more of an amine, thiol, acrylate,alkyne, maleimide, silane, azide, hydroxyl, lipid, disulfide,fluorescent molecule, and/or biotin. In one embodiment, theconcentration stabilizing agent is a carbohydrate derivative. In variousembodiments, the polymer is a monosaccharide, a disaccharide, anoligosaccharide, a polysaccharide, and/or dextran. In variousembodiments, the dextran has a molecular weight that is less than about2,000 Dalton (e.g., 200-1,400, 1,000-1,900 Dalton), between about 2,000Dalton and 5,000 Dalton (e.g., 3,000-3,500, 2,000-4,000 Dalton), and/ormore than about 5,000 Dalton (e.g., 6,000-8,000, 7,000-13,000 Dalton).

In various embodiments, the concentration stabilizing chemical agent isany one or more of a phenol, a monomeric phenol, a dimeric phenol, atrimeric phenol, a polyphenol, a tannic acid, is gum Arabic, abiological molecule, a protein, a bovine serum albumin, streptavidin,biotin, a peptide, an oligonucleotide, a naturally occurringoligonucleotide, a synthetic oligonucleotide, a metal or metalloidoxide, and/or a silicon dioxide shell. In one embodiment, a silicondioxide shell has ranges in thickness from about less than 1 nm to about100 nm (e.g., 10-70, 30-90, 40-60 nm). In one embodiment, a combinationof stabilizing agents are used. In various embodiments, the solvent canbe one or more of water, an alcohol, ethanol, isopropyl alcohol,t-butanol, a mixture of a water and an alcohol.

In one embodiment, the concentration of silver nanoplates is increasedusing tangential flow filtration. In one embodiment, the tangential flowfiltration is performed using a tangential flow filter membrane. In oneembodiment, the tangential flow membrane is made from a cellulose esteror mix of cellulose esters. In various embodiments, the tangential flowmembrane is made from one or more of polyetheresulfone and/orpolysulfone. In various embodiments, the tangential flow membrane has amolecular weight cut off of less than about 10 kD (e.g., 1-5, 8 kD), ofbetween about 10 kD and 500 kD (e.g., 50-250, 300-400 kD), of more thanabout 500 kD (e.g., 750, 1000, 5000 kD or more), of less than about 0.05μm, of between about 0.05 μm and 0.5 μm (e.g., 0.01, 0.03 μm), and/or ofmore than about 0.5 μm (e.g., 1.0, 2, 5, 10, 100 μm).

In various embodiments, the silver nanoplate solution is concentrated toproduce a solution with an optical density of greater than about 10 cm⁻¹(e.g., 15-45 cm⁻¹, 30-150 cm⁻¹, or more), greater than about 50 cm⁻¹(e.g., 80-150 cm⁻¹, 60-120 cm⁻¹, 100 cm⁻¹ or more), greater than about75 cm⁻¹ (e.g., 80-110 cm⁻¹, 200-400 cm⁻¹, 1000 cm⁻¹ or more), greaterthan about 100 cm⁻¹ (e.g., 150-350 cm⁻¹, 200-400 cm⁻¹ or more), and/orgreater than about 500 cm⁻¹ (e.g., 600-1500 cm⁻¹, 1000 cm⁻¹ or more).

In one embodiment, the solvent of the concentrated solution is exchangedusing tangential flow filtration. In one embodiment, the concentratedsolution is processed to remove residual chemicals using tangential flowfiltration.

In various embodiments, a solution of nanoparticles comprising silvernanoparticles is coated with a polymer with an optical density greaterthan 100 cm⁻¹ (e.g., 160-550 cm⁻¹, 900-1100 cm⁻¹, 100 cm⁻¹, 1000 cm⁻¹ ormore).

In one embodiment, the solution of silver nanoplates is incubated with asubstrate (e.g., fibers, cloth, mesh, bandages, socks, wraps, otherarticles of clothing, sponges, high porosity substrates, particles withedge lengths greater than 1 micron, beads, hair, skin, paper, absorbentpolymers, foam, wood, cork, slides, roughened surfaces, biocompatiblesubstrates, filters, and/or medical implants). In one embodiment, thesubstrate is removed from the solution of silver nanoplates and dried.

BRIEF DESCRIPTION OF THE DRAWINGS

Further objects, features and advantages of the invention will becomeapparent from the following detailed description taken in conjunctionwith the accompanying figures showing illustrative embodiments of theinvention, in which the following is a description of the drawings. Thedrawings are examples, and should not be used to limit the embodiments.Moreover, recitation of embodiments having stated features is notintended to exclude other embodiments having additional features orother embodiments incorporating different combinations of the statedfeatures. Further, features in one embodiment (such as in one figure)may be combined with descriptions (and figures) of other embodiments.

FIG. 1 illustrates the optical spectrum of a silver nanoplate solutionas fabricated using a photoconversion method according to one embodimentof the present invention. In one embodiment, a silver nanoplate solutionis fabricated using a photoconversion method identified as [DSS1099,alternative spectrum ARS1134]—as fabricated, these silver nanoplateshave an optical density of less than 1 cm⁻¹.

FIG. 2 illustrates a transmission electron micrograph of silvernanoplates fabricated using a photoconversion method according to oneembodiment of the present invention. Scale bar is 50 nm.

FIG. 3 illustrates one embodiment of plates concentrated in the absenceof a concentration stabilizing agent with normalized (bottom) andunnormalized (top) extinction spectra of as-fabricated silver nanoplatesbefore and after tangential flow filtration concentration. Afterconcentration the plates have a significantly changed peak shape asdemonstrated by the normalized plot, and a spectral peak at 400 nm thatdemonstrates that a large number of silver nanoplates have turned intosilver nanospheres. In one embodiment, plates are concentrated with theidentification [MGM1201 and 1195E].

FIG. 4 illustrates one embodiment of plates concentrated in the presenceof a concentration stabilizing agent with normalized (bottom) andunnormalized (top) extinction spectra of as-fabricated silver nanoplatesbefore and after tangential flow filtration concentration using aconcentration stabilizing agent. After being concentrated the platesretain their spectral peak shape with no increase in the spectral peakat 400 nm. In one embodiment, plates are concentrated with theidentification [MGM1282 and 1279A].

FIG. 5 illustrates extinction spectra of high optical density nanoplatesolutions processed using the methods described in various embodimentsof the invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

Several embodiments of the present invention comprise processes formaking solutions of plasmonic nanoparticle including silver nanoplatesthat are suitable for performing treatment of a target body region(e.g., such as for tumor ablation, hair removal, acne treatment, woundhealing, and antimicrobial applications). Optical Density (O.D.) is thelogarithmic ratio of the radiation incident on a material to theradiation transmitted through the material (O.D.=−log₁₀(I₁/I₀) where I₁is the intensity of transmitted light and I₀ is the intensity of theincident light). For solutions, the optical density is a function of thepath length through the liquid sample is expressed in units of cm⁻¹. Insome instances, optical density is expressed without the unit cm⁻¹—suchas in instances in which a standard path length of 1 cm is used.

Silver Nanoplate Physical Description

In one embodiment, silver nanoplates are characterized by lengths alongthe three principle axes wherein: the axial length of two of theprinciple axes is at least two times greater than the axial length ofthe shortest principle axis and the shortest principal axial length isless than about 500 nm.

The ratio of the average of the two longer principle axes to the shorterprinciple axes is referred to as the aspect ratio. In one embodiment theaverage aspect ratio of the silver plates is greater than 1.5, 2, 3, 4,5, 7, 10, 20, 30, or 50, or any range therein (e.g., greater than 8, 9,11, 12, 13, 14, 15, 25, 35, 40, 45). In various embodiments the averageaspect ratio of the silver plates is between 1.5 and 25, 2 and 25, 1.5and 50, 2 and 50, 3 and 25, or 3 and 50 (e.g., 5 and 20, 10 and 15, 5and 40, 5 and 30, 5 and 20, 10 and 50, 20 and 50, 30 and 50, 40 and 50,10 and 20, 20 and 30, 30 and 40, 40 and 50, and any values between 1.5and 50, inclusive).

In one embodiment the nanoplate has edge lengths less than 500 nm, 250nm, 200 nm, 150 nm, 100 nm, 80 nm, 60 nm or 50 nm (e.g., 400 nm, 300 nm,225 nm, 175 nm, 125 nm, 90 nm, 70 nm, 55 nm, and any values between 500and 50 nm, inclusive). In one embodiment the nanoplate has edge lengthsgreater than 5 nm, 10 nm, 20 nm, 30 nm, 50 nm or 100 nm, or any valuetherein or more (e.g., 15, 25, 40, 60, 70 75, 80, 90, 5-100, 20-80,30-50, 45-95 nm, and/or 30 nm to 100 nm, 20 nm to 150 nm, 10 nm to 200nm, 10 nm to 300 nm). In one embodiment the nanoplate has a thickness(third principle axis) that is less than 500 nm, 300 nm, 200 nm, 100 nm,80 nm, 60 nm, 50 nm, 40 nm, 30 nm, 20 nm, or 10 nm, or any value therein(e.g., 400 nm, 250 nm, 150 nm, 75 nm, 5 nm to 20 nm, 5 nm to 30 nm, 10nm to 30 nm, 10 nm to 50 nm, 10 nm to 100 nm).

Silver nanoplates have a variety of different cross sectional shapesincluding circular, triangular, or shapes that have any number ofdiscrete edges. In one embodiment the nanoplates have less than 20, 15,10, 8, 6, 5, or 4 edges (e.g., 18, 12, 11, 9, 2, 1). In one embodimentthe nanoplates have more than 2, 3, 4, or 5 edges (e.g., 6, 7, 10, 15,20 or more). In some embodiments the silver nanoplates have sharpcorners and in other embodiments the corners are rounded. In someembodiments of silver nanoplates, there are a variety of different crosssectional shapes within the same sample. In other embodiments of silvernanoplate solutions greater than 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%,80%, or 90% of the number of particles in solution are silver nanoplateswith the other particles having different shapes including but notlimited to spherical, cubic, and irregular. In one embodiment thenanoplates have one or two flat sides. In another embodiment thenanoplates are pyramidal.

Silver Nanoplate Fabrication

The silver nanoplates utilized in various embodiments of this inventionmay be fabricated using photoconversion (Jin et al. 2001; Jin et al.2003), pH controlled photoconversion (Xue 2007), thermal growth (Hao etal. 2004; Hao 2002; He 2008; Metraux 2005), templated growth (Hao et al.2004; Hao 2002), seed mediated growth (Aherne 2008; Chen; Carroll 2003;Chen; Carroll 2002, 2004; Chen et al. 2002; He 2008; Le Guevel 2009;Xiong et al. 2007), or alternative methods. Alternative methods includemethods in which the silver nanoplates are formed from a solutioncomprising a shape stabilizing agent or agents and a silver source, andin which chemical agents, biological agents, electromagnetic radiation,or heat are used to reduce the silver source.

FIG. 1 illustrates the optical spectrum of a silver nanoplate solutionas fabricated using a photoconversion method according to one embodimentof the present invention. In one embodiment, a silver nanoplate solutionis fabricated using a photoconversion method identified as [DSS1099,alternative spectrum ARS1134]—as fabricated, these silver nanoplateshave an optical density of less than 1 cm⁻¹.

FIG. 2 illustrates a transmission electron micrograph of silvernanoplates fabricated using a photoconversion method according to oneembodiment of the present invention. In FIG. 2, the scale bar is 50 nm.

FIG. 3 illustrates one embodiment of plates concentrated in the absenceof a concentration stabilizing agent with normalized (bottom) andunnormalized (top) optical extinction spectra of as-fabricated silvernanoplates before and after tangential flow filtration concentration.After concentration the plates have a significantly changed peak shapeas demonstrated by the normalized plot, and a spectral peak at 400 nmthat demonstrates that a large number of silver nanoplates have turnedinto silver nanospheres. In one embodiment, plates are concentrated withthe identification [MGM1201 and 1195E].

FIG. 4 illustrates one embodiment of plates concentrated in the presenceof a concentration stabilizing agent with normalized (bottom) andunnormalized (top) optical extinction spectra of as-fabricated silvernanoplates before and after tangential flow filtration concentrationusing a concentration stabilizing agent. After being concentrated theplates retain their spectral peak shape with no increase in the spectralpeak at 400 nm. In one embodiment, plates are concentrated with theidentification [MGM1282 and 1279A].

FIG. 5 illustrates optical extinction spectra of high optical densitynanoplate solutions processed using the methods described in variousembodiments of the invention.

Silver Nanoplate Coating

In one embodiment, silver nanoplates have molecules that are adsorbed orotherwise bound to the particle surface. The molecules on the surfaceare the reactants or reactant by-products of the synthesis. One objectof one embodiment of this invention is to partially or fully exchangethe molecules that are bound to the surface of the silver nanoplateswith other molecules that more fully protect the particles from changingshape during concentration. Another object of one embodiment of theinvention is to use a stabilizing agent during fabrication thatgenerates plate shapes and also stabilizes the nanoplates duringsubsequent concentration.

In various embodiments, stabilizing agent variants that may be utilizedinclude chemical or biological agents that are physisorbed to thesurface, molecularly bound to the surface through specific interactions(e.g. thiol or amine), or encapsulate the surface (i.e. a metal oxide ormetalloid oxide shell). In various embodiments, specific chemical agentsof interest include polymers such as polysulphonates, vinyl polymers,carbohydrates, ethylene oxides, phenols, and carbohydrates. In variousembodiments, specific examples of these polymers include poly(sodium)styrene sulfonate, polyvinyl alcohol, polyvinyl pyrrolidone, tannicacid, dextran, and polyethylene glycol (PEG) including PEG moleculeswhich contain one or more chemical groups (e.g. amine, thiol, acrylate,alkyne, maleimide, silane, azide, hydroxyl, lipid, disulfide,fluorescent molecule, or biomolecule moieties). In various embodiments,specific biomolecules of interest include proteins, peptides, andoligonucleotides, including biotin, bovine serum albumin, streptavidin,neutravidin, wheat germ agglutinin, naturally occurring and syntheticoligonucleotides and peptides, including synthetic oligonucleotideswhich have one or more chemical functionalities (e.g. amine, thiol,dithiol, acrylic phosphoramidite, azide, digoxigenin, alkynes, orbiomolecule moieties). Specific encapsulating chemical agents ofinterest include metal oxide shells such as SiO₂ and TiO₂. Stabilizingagents may be added prior to the formation of silver nanoplates, duringthe formation of silver nanoplates, or after the formation of silvernanoplates. An additional chemical agent of interest is gum arabic.

Carrier Solutions

In one embodiment of this invention the silver nanoplates are fabricatedin aqueous solutions. In other embodiments the silver nanoplates arefabricated in other solutions that can include ethanol, isopropanol, ororganic solvents such as heptane, toluene, or butanol.

In one embodiment an acid, base or buffering agent (e.g., a buffer) isadded to change the solution pH either before, during, or after theaddition of a stabilant. In various embodiments, the nanoplates aresuspended in a sodium bicarbonate buffer or a sodium borate buffer.

Surface Stabilization

In various embodiments, stabilizing agents can be solid or liquidformulations that are added to the silver plate solution. Thestabilizing agents have an affinity for the surface of the silvernanoplates and will associate with the plate surface. In someembodiments, the bound molecules on the silver nanoplates will bedisplaced by the added stabilizing agents. In some embodiments thestabilants are added to the as-fabricated silver nanoplate solution. Inother embodiments, the solution of nanoplates is washed, or the residualreactants are otherwise removed. In other embodiments, the suspendingsolution is exchanged with a different suspending media which includesethanol, isopropanol, or other polar or non-polar liquids before thestabilizing agents are added.

Once the stabilizing agent is added, the mixture of the stabilant andthe silver nanoplates can undergo a number of different processesincluding heating, boiling, boiling under reflux, rotoevaporation,vacuum, stirring, stirring with magnetic stir bars, stirring withoverhead mixers, stirring with homogenizers, shaking, microfluidization,refrigeration, and freezing.

Washing and Concentrating

In one embodiment, after the stabilization step is complete, the silvernanoplates can be washed to remove residual reactants or to exchange thesolution with another solution. In various embodiments, the exchange ofsolution can be accomplished using dialysis, centrifugation, filtration,or tangential flow filtration. One embodiment of the invention is wherethe number of wash volumes exchanged within the sample is 1, 2, 3, 4, 5,between 1 and 5, between 5 to 10, between 10 to 20, or more than 20 washvolumes.

High optical density solutions of the nanoparticles can be fabricatedusing centrifugation, evaporation, filtration, dialysis or tangentialflow filtration. One embodiment of this invention utilizes tangentialflow filtration as the process of concentrating the silver nanoplatesolution. The filter membrane utilized may be formed from a variety ofmaterials. Specific filter membrane materials of interest includecellulose esters, polysulfone, and polyetheresulfone. The filtermembrane utilized may have pores with a molecular weight cutoff of lessthan about 10 kD, between 10 kD to 500 kD, or more than about 500 kD(e.g., between 10 kD, to 100 kD, 10 kD to 500 kD, 20 kD to 500 kD, 20 kDto 250 kD), and/or pore sizes of less than about 0.05 μm, between 0.05μm and 0.5 μm, or larger than about 0.5 μm (e.g., between 0.02 μm and0.1 μm, 0.05 μm and 0.2 μm, 0.05 μm and 0.5 μm, 0.10 μm and 0.2 μm, 0.1μm and 0.5 μm). Tangential flow filtration can also be utilized tochange the solvent in which the silver nanoplates are dispersed.Specific solvents of interest include water and alcohols (e.g.t-butanol, ethanol, and isopropyl alcohol), as well as other polar ornon-polar solvents. Additionally, tangential flow filtration can beutilized to remove residual chemicals.

This invention includes embodiments in which the silver nanoplatesolution concentration is increased to produce a final solution withoptical densities of greater than about 5 cm⁻¹, greater than about 10cm⁻¹, greater than about 50 cm⁻¹, greater than about 75 cm⁻¹, greaterthan about 100 cm⁻¹, greater than about 500 cm⁻¹, or greater than about1000 cm⁻¹ (e.g., between 10 cm⁻¹ to 100 cm⁻¹, 30 cm⁻¹ to 300 cm⁻¹, 50cm⁻¹ to 500 cm⁻¹, 100 cm⁻¹ to 1000 cm⁻¹, 300 cm⁻¹ to 3000 cm⁻¹, or 500cm⁻¹ to 5000 cm⁻¹) One embodiment of the invention is where the silvernanoplate solution concentration is increased to above 10⁶, 10⁷, 10⁸,10⁹, 10¹⁰, 10¹¹, 10¹², 10¹³ particles per milliliter.

Storage

One embodiment of the invention is where the concentrated particles arestored at temperatures below −10, 0, 4, 6, 10, or 20 degrees C.

One embodiment of the invention is where the particles are frozen anddried under vacuum. One embodiment is where the particles are freezedried. One embodiment is where the particles are supercritically dried.Another embodiment is where an additional stabilant or othercryoprotectant is added to the solution before the particles are heatdried or freeze dried.

Composites

In one embodiment of the invention, high optical density solutions ofsilver nanoplates are associated with a substrate. Examples ofsubstrates include fibers, cloth, mesh, bandages, socks, wraps, otherarticles of clothing, sponges, high porosity substrates, particles withdiameters greater than 1 micron, beads, hair, skin, paper, absorbentpolymers, foam, wood, cork, slides, roughened surfaces, biocompatiblesubstrates, filters, or medical implants. In one embodiment, the highoptical density solutions of silver nanoplates at a concentration of atleast 1 mg/mL, 10 mg/mL, 100 mg/mL (e.g., 1 to 10, 3 to 30, 5 to 50, 10to 20, 5 to 50, 3 to 50, 1 to 100 mg/mL, 10 to 100, 20 to 100, 30 to 100mg/mL) are incubated with the substrate. In another embodiment, the highoptical density solutions of silver nanoplates at a concentration of atleast 1 mg/mL, 10 mg/mL, or 100 mg/mL (e.g., 1 to 10, 3 to 30, 5 to 50,10 to 20, 5 to 50, 3 to 50, 1 to 100 mg/mL, 10 to 100, 20 to 100, 30 to100 mg/mL) are incubated with the substrate. In another embodiment thesilver nanoplates are prepared at an optical density of at least 10,100, 300, 500, 1000, or 2000 cm⁻¹ (e.g., between 10-100, 20-200, 30-300,50-500, 100-1000, 200-1000, 300-1000, 500-1000, or 200-2000 cm⁻¹) beforeincubating with the substrate. In another embodiment the substrate ischemically treated to increase the binding of the nanoplates to thesubstrate. For example, the substrate could be functionalized with amolecule that yielded a positively or negatively charged surface. Inanother embodiment, the pH of the incubating solution is selected inorder to optimize binding. In another embodiment, the silver nanoplatescover at least 5%, 10%, 20%, 30%, 50% or 75% of the substrate (e.g., 5%to 10%, 10% to 100%, 10% to 50%, 50% to 100%, 30% to 100%, 30% to 70%,40% to 80%, 50% to 90%, 60% to 100%, 70% to 100%, 80% to 100%, 90% to100%, 0% to 5%, 1% to 10%, 2% to 20%, 5% to 30%, and/or 1% to 50% of thesubstrate). In another embodiment, other solvents or chemicals are addedto the incubation solution. In another embodiment a biological linker(e.g. antibodies, peptides, DNA) is used to bind the high opticaldensity silver nanoplates to the surface of the substrate. In oneembodiment, the incubation is for less than 1 minute, 5 minutes, 20minutes, 60 minutes, or 120 minutes (e.g., 0 to 1 minute, 1 minute to120 minutes, 5 minutes to 120 minutes, 20 minutes to 120 minutes, 60minutes to 120 minutes, 5 minutes to 60 minutes, 10 minutes to 60minutes, 20 minutes to 60 minutes, 0 minutes to 10 minutes, 0 minutes to20 minutes, or 0 minutes to 5 minutes).

In one embodiment, the substrate is separated from the incubatingsolution and dried. The substrate can be dried using air drying, heatdrying, freeze drying, or supercritical drying. In another embodimentthe dried substrate can be further processed by soaking the substrate inanother material, painting the substrate with another material, orexposing the substrate to another material that is in the vapor phase.

Other embodiments of the invention will be apparent to those skilled inthe art from consideration of the specification and practice of theinvention disclosed herein. It is intended that the specification andexamples be considered as disclosing certain embodiments of theinvention only, with a true scope and spirit of the invention beingindicated by the following claims.

The subject matter described herein may be embodied in other specificforms without departing from the spirit or essential characteristicsthereof. The foregoing embodiments are therefore to be considered in allrespects illustrative rather than limiting. While embodiments aresusceptible to various modifications, and alternative forms, specificexamples thereof have been shown in the drawings and are hereindescribed in detail. It should be understood, however, that theinvention is not to be limited to the particular forms or methodsdisclosed, but to the contrary, the invention is to cover allmodifications, equivalents, and alternatives falling within the spiritand scope of the various embodiments described and the appended claims.Any methods disclosed herein need not be performed in the order recited.

The methods disclosed herein include certain actions taken by apractitioner; however, they can also include any third-party instructionof those actions, either expressly or by implication. For example,actions such as “identifying a target region of skin tissue” include“instructing the identification of a target region of skin tissue.”

The ranges disclosed herein also encompass any and all overlap,sub-ranges, and combinations thereof. Language such as “up to,” “atleast,” “greater than,” “less than,” “between,” and the like includesthe number recited. Numbers preceded by a term such as “about” or“approximately” or “substantially” include the recited numbers. Forexample, “about 3 mm” includes “3 mm.” The terms “approximately”,“about” and/or “substantially” as used herein represent an amount orcharacteristic close to the stated amount or characteristic that stillperforms a desired function or achieves a desired result. For example,the terms “approximately”, “about”, and “substantially” may refer to anamount that is within less than 10% of, within less than 5% of, withinless than 1% of, within less than 0.1% of, and within less than 0.01% ofthe stated amount or characteristic.

EXAMPLES

Modern nanoparticle synthesis techniques have enabled the development ofmaterials with unique optical properties for a wide range ofapplications including diagnostic, obscurant, and therapeuticapplications. When as-fabricated nanoplates are concentrated usingtangential flow filtration, the shape many of the plates shift tonanospheres, reducing the formulation efficacy, as evidenced by theincreased peak height at 400 nm. By exchanging the surface capping agentof as-fabricated silver nanoplates with an agent that provides stabilitybefore, during, and/or after concentration, the silver nanoplates can beconcentrated to increase the solution optical density withoutdestabilizing the plates and degrading the beneficial opticalproperties.

The description of specific examples below are intended for purposes ofillustration only and are not intended to limit the scope of theinvention disclosed herein.

Example 1

15 L of silver nanoplates with a peak optical density of about 5 cm⁻¹were mixed with 3.5 g of polyvinylalcohol (PVA), and concentrated usingtangential flow filtration using a 500 kD polysulfone tangential flowmembrane with 3100 cm² of surface area. The solution was concentratedfor approximately 90 minutes, and the final solution volume was reducedfrom 15 L to 0.5 L. The increase of the silver nanoplate solutionoptical density was from 5 to about 150 cm⁻¹. Thus, according to oneembodiment, a method for increasing a silver nanoplate solution from 5cm⁻¹ to 150 cm⁻¹ (e.g., an increase of roughly 30 times the opticaldensity) comprises the steps of adding PVA to silver nanoplates, andconcentrating the solution with tangential flow filtration.

Example 2

1.2 L of silver nanoplates with a peak optical density of about 4 cm⁻¹were mixed with 4 L of anhydrous ethanol and about 49 mL of ammoniumhydroxide solution. 0.6 mL of a dilute aminopropyltriethoxysilane(APTES) was added to the solution. After 15 minutes of incubation, 6.5mL of tetraethylorthosilicate (TEOS) solution was added. After 24 hours1 L of the solution was concentrated using a 500 kD polysulfonetangential flow membrane with 1050 cm² of surface area. The finalsolution volume was decreased to 150 mL, increasing the silvernanoparticle solution optical density to about 40 cm⁻¹. Thus, accordingto one embodiment, a method for increasing a silver nanoplate solutionfrom 4 cm⁻¹ to 40 cm⁻¹ (e.g., an increase of roughly 10 times theoptical density) comprises the steps of adding anhydrous ethanol,ammonium hydroxide solution, aminopropyltriethoxysilane (APTES), andtetraethylorthosilicate (TEOS) to the silver nanoplates, andconcentrating the solution with tangential flow filtration.

Example 3

A 40 mL solution of 40 O.D. solution of concentrated silver nanoplateswas spun at 3000 RCF for 30 minutes. This processed was used toconcentrate the silver nanoplates to an optical density of 1000 O.D.

Example 4

A 5 mL solution of 1000 OD silver nanoplates was added to a 3″×3″section of absorbant cloth (Absorber Synthetic Drying Chamois, CleanTools). After addition, the substrate was allowed to air dry. Oncedried, the silver nanoplates were bound to the surface of the absorbantcloth and were not released when the cloth was subsequently wet andwater removed by applying pressure.

REFERENCES

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Each of the references listed above is incorporated by reference in itsentirety.

What is claimed is:
 1. A process for generating a solution of silvernanoplates with extremely high optical density comprising the steps of:a. Adding a concentration stabilizing chemical agent to a solution ofsilver nanoplates or precursor reagents. b. Increasing the concentrationof silver nanoplates to increase the optical density of the solution.